The overall aim of this proposal is to investigate the role of the monokine, endogenous pyrogen (EP), in human immunoregulation. While the physiologic role of this molecule in the pathogenesis of febrile responses has long been recognized, its function in the modulation of immunocompetent cell effects has only recently been evaluated. Methods for physicochemical characterization of EP allow for confident evaluation of its precise actions in cellular immune function. Results derived from this line of investigation may provide a better insight into the basic control mechanisms of immunity and may lead to a better understanding of the role of mononuclear phagocytes in immune function. The potential clinical relevance of this work is profound and could provide information regarding the interplay of fever and immune response in multiple diseases and conditions where fever is a prominent manifestation of illness. The specific areas of reasearch will include: 1) The role of EP in the activation and function of both human T and B lymphocytes. In vitro models of lymphocyte function will be studied and characterized in the light of EP effects. 2) Investigation into the mechanisms and cellular site of action of EP in immune cell function. Studies here will include EP effect on cellular metabolism (cyclic nucleotide and prostaglandin physiology), cell surface marker expression by immune cells (Ia, etc.), and cell membrane effects.